Novosti
Khirurgii
This journal is
indexed in Scopus



Year 2019 Vol. 27 No 2

REVIEWS

DOI: https://dx.doi.org/10.18484/2305-0047.2019.2.196   |  

I.V. MAIBORODIN 1, A.I. SHEVELA 1, V.V. MOROZOV 1, T.V. MIKHEEVA 1, N.F. FIGURENKO 1, R.V. MASLOV 1, V.I. MAIBORODINA 2

THE INFLUENCE OF EXTRACELLULAR VESICLES (EXOSOMES) OF MESENCHYMAL STROMAL CELLS ON BONE TISSUE REGENERATION

Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences, Siberian Branch 1,
Institute of Molecular Pathology and Pathomorphology, Federal Research Center for Fundamental and Translational Medicine 2,
Novosibirsk,
The Russian Federation

Mesenchymal stem/stromal cells (MSC) have been widely used for tissue regeneration including the repair of bone defects. However, shortcomings of MSC application, including the limited term of existence in tissues, have become an obstacle for further direct transplantation of MSC.
There is a necessary to create new methods of cell therapy that do not have the disadvantages of the direct MSC application, but which influence the bone tissue regeneration with the same effectiveness.
Cells influence each other and exchange the functional proteins and genetic material through the secretion of exosomes which can be also applied for the impact on tissue regeneration. Exosomes strengthen proliferation, migration and act as the inductors of differentiation of MSC in the determined direction including osteogenic one that leads to the considerable acceleration of bone defect reparation. The delivery of microRNA and various regulating cytokines is a possible mechanism of optimization of tissue reparation by exosomes. The action of exosomes to a large extent is similar to effects of MSC. The creation of animals with preset properties has good prospects. However, the assessment of therapeutic potential and use in future clinical tests of the extracellular vesicles secreted by various cells, demands their total characteristic, standardization of strictly particular conditions of storage and receiving, removal xenogenic and others substances, bound to the source.
The application of exosomes has high potential for reparative medicine, in particular, for acceleration of bone tissue regeneration, and opens new paths of medical research.

Keywords: regeneration of bone tissue, mesenchymal stromal cells, exosomes, microvesicles, cell interaction
p. 196-203 of the original issue
References
  1. Maiborodin IV, Matveyeva VA, Kolesnikov IS, Drovosekov MN, Toder MS, Shevela AI. Regeneration of the damaged mandibular bone in rat after the injection of autologous mesenchymal stem cells of bone marrow origin adsorbed on the fibrin clot. Morfologiia. 2011;140(6):79-85. https://elibrary.ru/download/elibrary_17112219_63292977.pdf (in Russ.)
  2. Lu Z, Chen Y, Dunstan C, Roohani-Esfahani S, Zreiqat H. Priming adipose stem cells with tumor necrosis factor-alpha preconditioning potentiates their exosome efficacy for bone regeneration. Tissue Eng Part A. 2017 Nov;23(21-22):1212-20. doi: 10.1089/ten.tea.2016.0548
  3. Takeda YS, Xu Q. Neuronal differentiation of human mesenchymal stem cells using exosomes derived from differentiating neuronal cells. PLoS One. 2015 Aug 6;10(8):e0135111. doi: 10.1371/journal.pone.0135111
  4. Pachler K, Lener T, Streif D, Dunai ZA, Desgeorges A, Feichtner M, Öller M, Schallmoser K, Rohde E, Gimona M. A Good manufacturing practice-grade standard protocol for exclusively human mesenchymal stromal cell-derived extracellular vesicles. Cytotherapy. 2017 Apr;19(4):458-72. doi: 10.1016/j.jcyt.2017.01.001
  5. Lener T, Gimona M, Aigner L, Börger V, Buzas E, Camussi G, Chaput N, Chatterjee D, Court FA, Del Portillo HA, O’Driscoll L, Fais S, Falcon-Perez JM, Felderhoff-Mueser U, Fraile L, Gho YS, Görgens A, Gupta RC, Hendrix A, Hermann DM, Hill AF, Hochberg F, Horn PA, de Kleijn D, Kordelas L, Kramer BW, Krämer-Albers EM, Laner-Plamberger S, Laitinen S, Leonardi T, Lorenowicz MJ, Lim SK, Lötvall J, Maguire CA, Marcilla A, Nazarenko I, Ochiya T, Patel T, Pedersen S, Pocsfalvi G, Pluchino S, Quesenberry P, Reischl IG, Rivera FJ, Sanzenbacher R, Schallmoser K, Slaper-Cortenbach I, Strunk D, Tonn T, Vader P, van Balkom BW, Wauben M, Andaloussi SE, Théry C, Rohde E, Giebel B. Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper. J Extracell Vesicles. 2015 Dec 31;4:30087. doi: 10.3402/jev.v4.30087
  6. Doeppner TR, Herz, Görgens A, Schlechter J, Ludwig AK, Radtke S, de Miroschedji K, Horn PA, Giebel B, Hermann DM. Extracellular vesicles improve post-stroke neuroregeneration and prevent postischemic immunosuppression. Stem Cells Transl Med. 2015 Oct;4(10):1131-43. doi: 10.5966/sctm.2015-0078
  7. Huang CC, Narayanan R, Alapati S, Ravindran S. Exosomes as biomimetic tools for stem cell differentiation: applications in dental pulp tissue regeneration. Biomaterials. 2016 Dec;111:103-15. doi: 10.1016/j.biomaterials.2016.09.029
  8. Narayanan R, Huang CC, Ravindran S. Hijacking the cellular mail: exosome mediated differentiation of mesenchymal stem cells. Stem Cells Int. 2016;2016:3808674. doi: 10.1155/2016/3808674
  9. Furuta T, Miyaki S, Ishitobi H, Ogura T, Kato Y, Kamei N, Miyado K, Higashi Y, Ochi M. Mesenchymal stem cell-derived exosomes promote fracture healing in a mouse model. Stem Cells Transl Med. 2016 Dec;5(12):1620-30. doi: 10.5966sctm.2015-0285
  10. Qin Y, Sun R, Wu C, Wang L, Zhang C. Exosome: a novel approach to stimulate bone regeneration through regulation of osteogenesis and angiogenesis. Int J Mol Sci. 2016 May 19;17(5). pii: E712. doi: 10.3390/ijms17050712
  11. Silva AM, Almeida MI, Teixeira JH, Maia AF, Calin GA, Barbosa MA, Santos SG. Dendritic cell-derived extracellular vesicles mediate mesenchymal stem/stromal cell recruitment. Sci Rep. 2017 May 10;7(1):1667. doi: 10.1038/s41598-017-01809-x
  12. Zhang J, Liu X, Li H, Chen C, Hu B, Niu X, Li Q, Zhao B, Xie Z, Wang Y. Exosomes/tricalcium phosphate combination scaffolds can enhance bone regeneration by activating the PI3K/Akt signaling pathway. Stem Cell Res Ther. 2016 Sep 20;7(1):136. doi: 10.1186/s13287-016-0391-3
  13. Zhang S, Chu WC, Lai RC, Lim SK, Hui JH, Toh WS. Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration. Osteoarthritis Cartilage. 2016 Dec;24(12):2135-40. doi: 10.1016/j.joca.2016.06.022
  14. Wang KX, Xu LL, Rui YF, Huang S, Lin SE, Xiong JH, Li YH, Lee WY, Li G. The effects of secretion factors from umbilical cord derived mesenchymal stem cells on osteogenic differentiation of mesenchymal stem cells. PLoS One. 2015 Mar 23;10(3):e0120593. doi: 10.1371/journal.pone.0120593. eCollection 2015.
  15. Qi X, Zhang J, Yuan H, Xu Z, Li Q, Niu X, Hu B, Wang Y, Li X. Exosomes secreted by human-induced pluripotent stem cell-derived mesenchymal stem cells repair critical-sized bone defects through enhanced angiogenesis and osteogenesis in osteoporotic rats. Int J Biol Sci. 2016 May 25;12(7):836-49. doi: 10.7150/ijbs.14809. eCollection 2016.
  16. Torreggiani E, Perut F, Roncuzzi L, Zini N, Baglìo SR, Baldini N. Exosomes: novel effectors of human platelet lysate activity. Eur Cell Mater. 2014 Sep 22;28:137-51; discussion 151. doi: 10.22203/eCM.v028a11
  17. Ekström K, Omar O, Granéli C, Wang X, Vazirisani F, Thomsen P. Monocyte exosomes stimulate the osteogenic gene expression of mesenchymal stem cells. PLoS One. 2013 Sep 18;8(9):e75227. doi: 10.1371/journal.pone.0075227. eCollection 2013.
  18. Namazi H, Mohit E, Namazi I, Rajabi S, Samadian A, Hajizadeh-Saffar E, Aghdami N, Baharvand H. Exosomes secreted by hypoxic cardiosphere-derived cells enhance tube formation and increase pro-angiogenic miRNA. J Cell Biochem. 2018 May;119(5):4150-60. doi: 10.1002/jcb.26621
  19. Selvasandran K, Makhoul G, Jaiswal PK, Jurakhan R, Li L, Ridwan K, Cecere R. A tumor necrosis factor-α and hypoxia-induced secretome therapy for myocardial repair. Ann Thorac Surg. 2018 Mar;105(3):715-23. doi: 10.1016/j.athoracsur.2017.09.005
  20. Gonzalez-King H, García NA, Ontoria-Oviedo I, Ciria M, Montero JA, Sepúlveda P. Hypoxia inducible factor-1α potentiates jagged 1-mediated angiogenesis by mesenchymal stem cell-derived exosomes. Stem Cells. 2017 Jul;35(7):1747-59. doi: 10.1002/stem.2618
  21. Hnatiuk AP, Ong SG, Olea FD, Locatelli P, Riegler J, Lee WH, Jen CH, De Lorenzi A, Giménez CS, Laguens R, Wu JC, Crottogini A. Allogeneic mesenchymal stromal cells overexpressing mutant human hypoxia-inducible factor 1-α (hif1-α) in an ovine model of acute myocardial infarction. J Am Heart Assoc. 2016 Jul 6;5(7). pii: e003714. doi: 10.1161/JAHA.116.003714
  22. Li H, Liu D, Li C, Zhou S, Tian D, Xiao D, Zhang H, Gao F, Huang J. Exosomes secreted from mutant-HIF-1α-modified bone-marrow-derived mesenchymal stem cells attenuate early steroid-induced avascular necrosis of femoral head in rabbit. Cell Biol Int. 2017 Dec;41(12):1379-90. doi: 10.1002/cbin.10869
Address for correspondence:
630090, The Russian Federation,
Novosibirsk, Ac. Lavrentyev Ave., 8,
Institute of Chemical Biology
and Fundamental Medicine SB RAS,
Center of New Medical Technologies.
Tel.: 8-913-753-0767,
e-mail: imai@mail.ru,
Igor V. Maiborodin
Information about the authors:
Maiborodin Igor V., MD, Professor, Chief Researcher of the Stem Cell Laboratory, Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences, Siberian Branch, Novosibirsk, Russian Federation.
http://orcid.org/0000-0002-8182-5084
Shevela Andrey I., MD, Professor, Head of the Center of Innovative Medical Technologies, Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences, Siberian Branch, Novosibirsk, Russian Federation.
http://orcid.org/0000-0002-3164-9377
Morozov Vitaly V., Head of the Laboratory of Invasive Medical Technologies, Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences, Siberian Branch, Novosibirsk, Russian Federation.
https://orcid.org/0000-0002-9810-5593
Mikheeva Tatiana V., PhD, Applicant for Doctors Degree of the Stem Cell Laboratory, Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences, Siberian Branch, Novosibirsk, Russian Federation.
http://orcid.org/0000-0003-2249-5174
Figurenko Nikolay F., PhD, Applicant for Doctors Degree of the Stem Cell Laboratory, Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences, Siberian Branch, Novosibirsk, Russian Federation.
http://orcid.org/0000-0002-0430-8673
Maslov Roman V., PhD, Applicant for Doctors Degree of the Stem Cell Laboratory, Institute of Chemical Biology and Fundamental Medicine, Russian Academy of Sciences, Siberian Branch, Novosibirsk, Russian Federation.
http://orcid.org/0000-0003-4472-859X
Maiborodina Vitalina I., MD, Leading Researcher of the Laboratory of Ultrastructural Basis of Pathology, Institute of Molecular Pathology and Pathomorphology, Federal Research Center for Fundamental and Translational Medicine, Novosibirsk, Russian Federation.
http://orcid.org/0000-0002-5169-6373
Contacts | ©Vitebsk State Medical University, 2007